Novel modalities for prostate cancer screening: mast cells as predictors of disease, disease aggressiveness and marks of disease disparity

前列腺癌筛查的新方法：肥大细胞作为疾病、疾病侵袭性和疾病差异标志的预测因子

• 批准号: 10650620
• 负责人: CAROLE A OSKERITZIAN
• 金额: $ 20.9万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10650620
• 关键词: Address; Affect; African American; Age; Aging; Area; Benign; Biological; Biological Markers; Biopsy; Biopsy Specimen; Cancer Patient; Caregivers; Cell Aggregation; Cell Count; Cells; Clinic; Collection; Complex; Core Biopsy; Data; Data Analyses; Development; Diagnosis; Diagnostic; Disease; Disparity; Doctor of Medicine; Early Diagnosis; Endowment; Ethnic Population; Evaluation; Faculty; Feasibility Studies; Future; Gene Expression Profiling; Genes; Goals; Grant; Health; Human; Hypersensitivity; Image; Image Analysis; Incidence; Laboratories; Lesion; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Medical; Methods; Modality; Molecular; Molecular Profiling; Morbidity - disease rate; Mus; Nature; Normal tissue morphology; Oncogenic; Oncologist; Patients; Phenotype; Physicians; Pilot Projects; Population; Positioning Attribute; Predictive Value; Predisposition; Prevention; Property; Prostate; Prostatic; Prostatic Tissue; Race; Research; Risk; Sampling; Screening for Prostate Cancer; Site; Solid Neoplasm; Source; Sphingolipids; Survey Methodology; Testing; Tissues; United States; Urology; Variant; baby boomer; cancer diagnosis; cancer health disparity; caucasian American; clinically relevant; clinically significant; computerized; cost effective; disease disparity; first responder; functional status; high risk; human tissue; imaging modality; improved; innovation; insight; interest; mast cell; member; men; mortality; novel; overexpression; prisma; prostate biopsy; prostate cancer risk; quantitative imaging; racial disparity; racial population; screening; sphingosine 1-phosphate; success; tumor; urologic; validation studies

SUMMARY Prostate cancer (PCa) is the second most common cancer in men in the United States. The absolute number of men with PCa is projected to increase as a result of the ageing baby boomer population. However, the lack of reliable biomarkers for PCa screening has led to decreased early detection, particularly for African American (AA) men who have the highest PCa morbidity, metastatic risk and mortality rates than any other racial or ethnic group in the US. When cancer is suspected, patients must undergo multiple needle core biopsies because of the multifocal nature of PCa. Nonetheless, up to 34% of biopsied men are told they are cancer-free when they are not, because the biopsies missed the cancer foci. Hence, it is critical to better define the cellular and molecular features indicative of PCa development and risk for aggressive disease in benign biopsies of PCa patients to improve diagnosis and screening. In this grant, we are proposing to explore a variation on the concept of field effect in PCa, postulating that histopathologically benign looking prostate core biopsies may in fact feature alterations indicative of PCa and of PCa aggressiveness present in the same patient at another prostatic site, using age- and race-matched (AA and Caucasian Americans (CA)) sets of samples (benign and cancer-bearing biopsies for each patient). Prostate-resident mast cells (MC) aggregate in stromal, peritumoral and/or intratumoral areas but their clinical relevance remains controversial. Our preliminary data suggests the usefulness of establishing MC profiles in benign prostatic tissues of PCa patients. The objectives of this application are: to investigate MC functional profiles in benign human prostate tissues as predictors of PCa aggressiveness and candidate functional biomarkers of PCa race disparity; to define and validate a molecular signature indicative of PCa and PCa aggressiveness present in benign human prostate biopsies and test its predictive value for PCa disparity and association to MC; and apply our new screening modalities in clinics, contingent upon successful validation studies. We anticipate that our approach may improve diagnosis and screening for high-risk PCa and position MC as potential drivers of PCa disparity.

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